6ZYK

Non-heme monooxygenase, ThoJ-Ni complex

6ZYK の概要

• エントリーDOI: 10.2210/pdb6zyk/pdb
• 分子名称: Monooxygenase, NICKEL (II) ION, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: non-heme monooxygenase, metal binding protein
• 由来する生物種: Streptomyces malaysiense
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33787.15

構造登録者

Koehnke, J.,Sikandar, A. (登録日: 2020-08-02, 公開日: 2020-10-14, 最終更新日: 2024-01-31)

主引用文献

Sikandar, A.,Lopatniuk, M.,Luzhetskyy, A.,Koehnke, J.
Non-Heme Monooxygenase ThoJ Catalyzes Thioholgamide beta-Hydroxylation.
Acs Chem.Biol., 15:2815-2819, 2020

PubMed Abstract: Thioviridamide-like compounds, including thioholgamides, are ribosomally synthesized and post-translationally modified peptide natural products with potent anticancer cell activity and an unprecedented structure. Very little is known about their biosynthesis, and we were intrigued by the β-hydroxy-N1, N3-dimethylhistidinium moiety found in these compounds. Here we report the construction of a heterologous host capable of producing thioholgamide with a 15-fold increased yield compared to the wild-type strain. A knockout of , encoding a predicted nonheme monooxygenase, shows that ThoJ is essential for thioholgamide β-hydroxylation. The crystal structure of ThoJ exhibits a typical mono/dioxygenase fold with conserved key active-site residues. Yet, ThoJ possesses a very large substrate binding pocket that appears suitable to receive a cyclic thioholgamide intermediate for hydroxylation. The improved production of the heterologous host will enable the dissection of the individual biosynthetic steps involved in biosynthesis of this exciting RiPP family.

PubMed: 32965102
DOI: 10.1021/acschembio.0c00637

実験手法

X-RAY DIFFRACTION (2.55 Å)